Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment

Blood Cancer J. 2016 May 27;6(5):e428. doi: 10.1038/bcj.2016.37.

Abstract

Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Bortezomib / administration & dosage
  • Bortezomib / therapeutic use
  • Female
  • Humans
  • L-Selectin / blood
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • Prognosis
  • Recurrence
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Vascular Cell Adhesion Molecule-1 / blood*

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Vascular Cell Adhesion Molecule-1
  • L-Selectin
  • Thalidomide
  • Bortezomib
  • Lenalidomide